The brain is a highly differentiated organ which is particularly sensitive to the lack of oxygen and glucose. The neuronal synapse (both in situ and as isolated synaptosomes) has been chosen for this study because of its key in neurotransmission and its high metabolic requirement for oxygen. The behavior of the neuronal synapse in situ will be measured on the giant synapse of animals such as the larvae of Xenopus laevis using microelectrodes. These measurements will be compared with those on isolated rat brain synaptosomes (using other methods) under various conditions, including hypoxia, in order to ascertain the physiological relevance of the properties of isolated synaptosomes to the synapse in vivo. The isolated synaptosomes will be used to study: 1. The regulation of neuronal energy metabolism with special attention to the role of mitochondrial respiration. 2. Neurotransmitter uptake and metabolism and its relation to transmembrane electrical and pH gradients. 3. The oxygen dependence of the energy metabolism and its relation to the sensitivity of the brain to hypoxia.